Myocardial growth and hypertrophy are characterized by coordinate increases in myofibrillar protein content. The long term objective of this proposal is to delineate the molecular mechanisms which couple the hypertrophic stimulus with the accumulation of myofibrillar protein. Recent evidence obtained from skeletal muscle suggests that myofibrillar protein content and composition can be controlled at the level of myofibrillar gene expression; i.e., the transcription of mRNAs from the corresponding myofibrillar genes. The central hypothesis to be tested in this proposal is that the increase in myofibrillar protein content during cardiac growth and hypertrophy is due to an increase in the level of mRNAs which code for specific myofibrillar proteins. It is postulated that the level of a specific myofibrillar mRNA species is regulated by the rate of transcription from the corresponding myofibrillar gene(s). Thus, coordinate regulation of myofibrillar protein synthesis during cardiac growth and hypertrophy may be mediated by coordinate increases in myofibrillar gene transcription. In addition, we hypothesize that hydrolysis of phosphatidylinositol and/or the activation of protein kinase C may play a role in the generation and/or transmission of the hypertrophic response of cardiac muscle cells. Accordingly, the Specific Aims of this proposal are five fold: 1) to examine the correlation between changes in the level of an individual myofibrillar protein in a cultured cell model of myocardial growth and hypertrophy; 2) to determine if there is an increase in the rate of transcription of an individual myofibrillar gene and/or an increase in myofibrillar mRNA stability in a cultured myocardial cell model of growth and hypertrophy; 3) to determine if the rate of transcription of two separate myofibrillar genes is coordinately regulated in this model; 4) to determine if the rate of transcription of a non-myofibrillar gene is coordinately regulated with the transcription of myofibrillar genes in this cell model of cardiac mypertrophy; 5) to determine if the hydrolysis of phosphatidylinositol and/or the activation of protein kinase C are involved in coupling the hypertrophic stimulus to the increase in myofibrillar protein synthesis and associated alterations in myofibrillar gene expression.